Clinical and biochemical response to neridronate treatment in a patient with osteoporosis-pseudoglioma syndrome (OPPG)

Osteoporosis-pseudoglioma syndrome (OPPG) is a rare autosomal recessive syndrome characterized by juvenile-onset osteoporosis and ocular abnormalities due to a low-density lipoprotein receptor-related protein 5 (LRP5) gene mutation. Treatment with bisphosphonates, particularly with pamidronate and risedronate, has been reported to be of some efficacy in this condition. We report on a patient with OPPG due to an LRP5 gene mutation, who showed an encouraging response after a 36-month period of neridronate therapy. We report a case of a patient treated with bisphosphonates. Bisphosphonates should be administered in OPPG patients as a first-line therapy during early childhood

Serum creatine kinase isoenzymes in children with osteogenesis imperfecta

This study evaluates serum creatine kinase isoenzyme activity in children with osteogenesis imperfecta to determine its usefulness as a biochemical marker during treatment with bisphosphonate. The changes of creatine kinase (CK) isoenzyme activity during and after discontinuation therapy were observed. These results could be useful in addressing over-treatment risk prevention. Introduction The brain isoenzyme of creatine kinase (CKbb) is highly expressed in mature osteoclasts during osteoclastogenesis, thus plays an important role in bone resorption. We previously identified high serum CKbb levels in 18 children with osteogenesis imperfect (OI) type 1 treated for 1 year with bisphosphonate (neridronate). In the present study, serum CK isoenzymes were evaluated in the same children with continuous versus discontinued neridronate treatment over a further 2-year follow-up period. Methods This study included 18 children with OI type 1, 12 with continued (group A) and 6 with ceased (group B) neridronate treatment. Auxological data, serum biochemical markers of bone metabolism, bone mineral density z-score, and serum total CK and isoenzyme activities were determined in both groups. Results Serum CKbb was progressively and significantly increased in group A (p < 0.004) but rapidly decreased to undetectable levels in group B. In both groups, the cardiac muscle creatine kinase isoenzyme (CKmb) showed a marked decrease, while serum C-terminal telopeptide (CTx) levels were almost unchanged. Conclusions This study provides evidence of the cumulative effect of neridronate administration in increasing serum CKbb levels and the reversible effect after its discontinuation. This approach could be employed for verifying the usefulness of serum CKbb as a biochemical marker in patients receiving prolonged bisphosphonate treatment. Moreover, the decreased serum CKmb levels suggest a systemic effect of these drugs

Buoyant MHD flows in a vertical channel: the levitation regime

Buoyant magnetohydrodynamic (MHD) flows with Joulean and viscous heating effects are considered in a vertical parallel plate channel. The applied magnetic field is uniform and perpendicular to the plates which are subject to adiabatic and isothermal boundary conditions, respectively. The main issue of the paper is the levitation regime, i.e., the fully developed flow regime for large values of the Hartmann number M, when the hydrodynamic pressure gradient evaluated at the temperature of the adiabatic wall is vanishing. The problem is solved analytically by Taylor series method and the solution is validated numerically. It is found that the fluid velocity points everywhere and for all values of M downward. For small M's, the velocity field extends nearly symmetrically (with respect to the mid-plane) over the whole section of the channel between the adiabatic and the isothermal walls. For large values of M, by contrast, the fluid levitates over a broad transversal range of the channel, while the motion becomes concentrated in a narrow boundary layer in the neighborhood of the isothermal wall. Accordingly, the fluid temperature is nearly uniform in the levitation range and decreases rapidly within the boundary layer in front of the isothermal wall. It also turns out that not only the volumetric heat generation by the Joule effect, but also that by viscous friction increases rapidly with increasing values of M, the latter effect being even larger than the former one for all

Association between spondylolisthesis and L5 fracture in patients with osteogenesis imperfecta

To investigate if an association between spondylolisthesis and L5 fracture occurs in patients affected by Osteogenesis Imperfecta (O.I.). Methods Anteroposterior and lateral radiograms were performed on the sample (38 O.I. patients, of whom 19 presenting listhesis); on imaging studies spondylolisthesis was quantified according to the Meyerding classification. Genant’s semiquantitative classification was applied on lateral view to evaluate the L5 fractures; skeleton spinal morphometry (MXA) was carried out on the same images to collect quantitative data comparable and superimposable to Genant’s classification. The gathered information were analyzed through statistical tests (O.R., χ 2 test, Fisher’s test, Pearson’s correlation coefficient). Results The prevalence of L5 fractures is 73.7 % in O.I. patients with spondylolisthesis and their risk of experiencing such a fracture is twice than O.I. patients without listhesis (OR 2.04). Pearson’s χ 2 test demonstrates an association between L5 spondylolisthesis and L5 fracture, especially with moderate, posterior fractures (p = 0.017) and primarily in patients affected by type IV O.I. Conclusions Spondylolisthesis represents a risk factor for the development of more severe and biconcave/posterior type fractures of L5 in patients suffering from O.I., especially in type IV. This fits the hypothesis that the anterior sliding of the soma of L5 alters the dynamics of action of the load forces, localizing them on the central and posterior heights that become the focus of the stress due to movement of flexion–extension and twisting of the spine. As a result, there is greater probability of developing an important subsidence of the central and posterior walls of the soma

Donor species complement after liver xenotransplantation: The mechanism of protection from hyperacute rejection

Hamster hearts transplanted into stable rat recipients of hamster livers (OLT rats) were hyperacutely rejected after transfer with unaltered rat antihamster hyperimmune serum (HS). This was followed by immediate liver xenograft rejection in 4 of 5 rats. In contrast, simple heat inactivation of the rat HS resulted in prolonged survival of hamster hearts to 25 days without deterioration effect in the liver xenografts. This effect was species-specific because third-party mouse heart grafts in OLT rats were hyperacutely rejected in minutes if either active or heat inactivated antimouse HS was given. In cytotoxicity experiments, the complement in OLT serum produced weak lysis of hamster lymphocytes, while efficiently doing so with mouse cell targets. Because normal hamster serum caused no lysis at all of hamster target cells, the residual low-grade lysis of OLT serum was possibly being mediated by extrahepatic sources of rat C. In conclusion, the homology of C and target cells represents a mechanism of protection that the liver confers to other organs, and that is most easily seen in xenografts but may be allospecifically operational with allografts as well within the limits of MHC restriction. © 1994 by Williams and Wilkins